Our studies of amorphous calcium phosphate (ACP)-based dental materials (grant DE13169;initiated in the year 2000) were aimed to develop experimental bases/liners and orthodontic cements with moderate mechanical strength, good adhesiveness to tooth structures and pronounced potential to protect teeth from demineralization or even regenerate lost tooth mineral. Recently, a pit and fissure sealant, a crown and bridge cement and a light-cure orthodontic adhesive, all based on ACP/polymer technology developed in our group, have been made commercially available to dental practitioners. This continuing proposal focuses on design and evaluation of ACP composite materials intended for endodontic utility. The expected favorable biocompatibility of such composites is anticipated because of the design of resin systems with a high degree of conversion on polymerization (resulting in minimal leachables of organic species) and the chemical similarity of ACP to biological mineral. The bioactivity of the latter is due to the propensity of ACP to convert to thermodynamically stable apatite once exposed to oral milieu. The biocompatibility of the proposed new materials should be equal to, if not exceeding, the biocompatibility of currently utilized endodontic materials with the added benefit of ACP's long-lasting anti-cariogenic power. The main objectives are: [1] to assess the feasibility of formulating flowable, low-shrinking ACP composites with minimized leakage of unreacted monomers and/or degradation products and [2] to evaluate in vitro diffusion of material extracts through dentin barrier and assess their cytotoxicity. To achieve these goals we propose to: (a) formulate chemical cure and/or dual-cure resin capable of attaining high levels of vinyl conversion with the minimal adverse effect on shrinkage and/or stress developed upon polymerization, (b) create composites based on such resins with finely-dispersed ACP fillers, (c) evaluate physico-chemically both the unfilled resins (copolymers) and composites, (d) determine the movement of extracts of set materials across a dentin barrier, and (e) assess cellular response to copolymers and composites. The completion of the proposed research is expected to provide model material(s) suitable for endodontic clinical evaluation. In addition to the clinical impact, the studies may offer new experimental evidence still needed to better understand the polymer/filler and composite/tooth interphase phenomena as well as the cellular responses to these types of dental materials. Public Health Relevance: The proposed research on amorphous calcium phosphate (ACP)-based dental materials will: a)contribute to the basic understanding of the complex structure/property relationships in bioactive, remineralizing dental polymeric materials, and b) provide a model for the study of the demineralization/remineralization processes. An applicative aspect of this study is the design of an ACP endodontic sealer that would be both bioactive and biocompatible. Additionally, this technology may also lead to a bondable, remineralizing material that adheres to tooth structures and could mitigate root caries.